Cellular concepts of amyloid-beta seeding and spreading

• Applicant: Professorin Dr. Melanie Meyer-Luehmann
• Subject Area: Molecular and Cellular Neurology and Neuropathology ; Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2017
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 323695292

Olfactory dysfunction is an early symptom of dementia and has a high prevalence in various neurodegenerative diseases, reaching up to 90- 100% in AD. Senile plaques, the neuropathological hallmark of AD are encountered in the olfactory bulb of AD patients and in mouse models of AD, suggesting that it is among the first sites undergoing pathological changes. In general, the aggregation of Aβ is considered an essential early trigger in AD pathogenesis that leads to neurofibrillary tangles, neuronal dysfunction and dementia. However cellular mechanisms involved in the propagation/spreading of Aβ seeds are still elusive. The data obtained in the previous DFG project show that seeding in the olfactory bulb leads to olfactory deficits. However, our understanding how Aβ protein spreads through the brain from the olfactory bulb is still very limited. Therefore, the overall goal of this research project is to get a deeper understanding of Aβ spreading at the molecular, cellular and systems levels that will elucidate pathogenic mechanisms which will in turn pave the way to develop non-pharmacological preventive treatment strategies.

• DFG Programme: Research Grants